ABSTRACT We request funds to purchase a fully automated microscale thermophoresis (MST) instrument equipped with two detectors and a liquid handling robot. This instrument will be installed in the Department of Biochemistry as part of the newly created Program in Chemical Biology Medical College of Wisconsin. This Program builds on a strong history of providing shared biophysical instrumentation to a diverse group of NIH- funded investigators in Milwaukee and southeast Wisconsin since 2000. The MST instrument will play a pivotal role in the expansion of drug discovery on campus that has recently benefitted from over $5M investments in infrastructure and the commitment to hire 2-3 tenure-track faculty into the Program in Chemical Biology. Consistent with its record of major investments in biophysical research infrastructure and facilities, MCW has committed space to house the requested instrument, funds for service contracts, and salary support for technical staff to ensure training of the users and maintenance and repairs of the instrument. We describe projects from 5 major users with NIH funding and 6 minor users with NIH funding that will benefit from the requested instrumentation. The user projects span a range of biomolecular interaction and drug discovery studies on soluble and integral membrane proteins and their complexes with other proteins, nucleic acids, lipids, carbohydrates and other ligands. These projects will benefit from the fully automated MST instrument due to the increases in throughput and sensitivity that this technology affords. When installed, this instrument will be the only MST instrument in the State of Wisconsin. The Program in Chemical Biology is already equipped with the necessary infrastructure for successful installation and operation of this instrument. The new instrument will be maintained by PhD-level staff with experience in the operation and maintenance of multi- user biophysical instruments and robotics. Users will be trained in the operation of the MST and instrument time will be allocated using the existing PCB scheduling system via Google Calendar. A standing local advisory committee provides oversight of operations and conflict resolution. Acquisition of the MST instrument requested in this application will have a significant impact on NIH-funded biomedical research programs at MCW and other institutions in the region.!!